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Study of SXL01 in Patients With Metastatic Castration-Resistant Prostate Cancer (PROSTIRNA) (PROSTIRNA)

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ClinicalTrials.gov Identifier: NCT02866916
Recruitment Status : Not yet recruiting
First Posted : August 15, 2016
Last Update Posted : November 25, 2016
Sponsor:
Information provided by (Responsible Party):
Institut Claudius Regaud

Brief Summary:

This is a single site, open-label, non-randomized, dose escalation phase I study designed to evaluate the safety, the tolerability and the Recommended Phase II Dose (RP2D) of SXL01, a synthetic small interfering ribonucleic acid (RNA) targeting the androgen receptor messenger RNA (mRNA), in patients with metastatic castration-resistant prostate cancer.

A standard method "3+3" will be used for dose escalation. A maximum of 30 patients will complete the dose-escalation phase of the study; 12 additional patients will be included at the RP2D in the expansion phase.


Condition or disease Intervention/treatment Phase
Prostatic Cancer, Castration-Resistant Drug: SXL01 Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 42 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Study of SXL01 in Patients With Metastatic Castration-Resistant Prostate Cancer
Study Start Date : June 2017
Estimated Primary Completion Date : March 2020
Estimated Study Completion Date : March 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arm Intervention/treatment
Experimental: Dose escalation

The standard method "3+3" will be used for dose escalation: the first 3 patients will be treated at level 1; consecutive cohorts of 3 to 6 patients will be treated with increasing doses of SXL01.

Treatment will be administered until patient experiences unacceptable toxicity, PSA raising, progressive disease and/or treatment is discontinued at the discretion of the investigator or withdrawal of consent.

Additional patients will be included at the Recommended Phase II Dose (RP2D) in the expansion phase.

Drug: SXL01



Primary Outcome Measures :
  1. Incidence rate of Dose Limiting Toxicities (DLT) during the first cycle of treatment with SXL01. [ Time Frame: 25 months ]
  2. Characteristics of Dose Limiting Toxicities (DLT) during the first cycle of treatment with SXL01. [ Time Frame: 25 months ]
  3. Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: 33 months ]
    Tolerability and safety will be assessed through recording of adverse events using National Cancer Institute Common Terminology Criteria for Adverse Event (NCI-CTCAE) toxicity classification, monitoring biological parameters and vital signs measurement.


Secondary Outcome Measures :
  1. Preliminary efficacy endpoint : rate of patients presenting Prostate Specific Antigen (PSA) progression defined using Prostate Cancer Clinical Trial Working Group 3 (PCWG3) [ Time Frame: 33 months ]
  2. Preliminary efficacy endpoint : rate of patients presenting clinical or radiological progression using Response Evaluation Criteria in Solid Tumours (RECIST) V1.1 as defined by PCWG3. [ Time Frame: 33 months ]
  3. Pharmacokinetics - SXL01 plasma concentration [ Time Frame: Cycle 1: pre-dose (T0) then 0.5, 3, 6, 24 hours post dose on day 1 ; T0 on days 4, 8, 15, 22. Subsequent cycles : before administration on day 1 (CXD1). The day of treatment discontinuation (CXDX) : 0.5, 1, 2, 24 hours post-dose. ]


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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Males age 18-80 years.
  2. Eastern Cooperative Oncology Group (ECOG) performance status 0 - 1.
  3. Life expectancy of more than 3 months.
  4. Histologically confirmed prostate adenocarcinoma without neuroendocrine differentiation or small cell feature.
  5. Metastatic prostate cancer deemed to be unresponsive or refractory to hormone therapy.
  6. Detectable metastases by bone scan, Computerized tomography (CT) scan or Magnetic resonance imaging (MRI).
  7. Surgically or medically castrated, with testosterone levels of < 50 ng/dL (< 2.0 nM). If the patient is being treated with Luteinizing Hormone Releasing Hormone (LHRH) agonists (patient who have not undergone orchiectomy), this therapy must have been initiated at least 4 weeks prior to Cycle 1 Day 1 and must be continued throughout the study.
  8. Documented prostate cancer progression as assessed by the investigator with one of the following:

    8.1. PSA progression defined by a minimum of two raising PSA levels with an interval of >1 week between each determination. The PSA values at the screening visit must be ≥ 1 µg/l (1 ng/mL).

    8.2. Radiographic progression of soft tissue disease by modified RECIST criteria 1.1 or of bone metastasis with two or more documented new bone lesions on a bone scan with or without PSA progression.

  9. Adequate hepatic, renal, and hematologic function: aspartate transaminase (AST) / alanine transaminase (ALT) ≤ 2.5 X Upper Limit of Normal (ULN); Normal bilirubin or ≤ 1.5 ULN in case of Gilbert's syndrome; Serum creatinine Clearance > 60 mL/min by the Cockcroft-Gault formula; Hemoglobin ≥ 10 g/dL; Absolute neutrophil count ≥ 1500/mm3, Platelet count ≥ 100,000/mm3.
  10. Patients must have recovered from the toxic effects of prior therapy (except alopecia) to National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03 grade ≤1 and to baseline laboratory values as defined in inclusion criteria 9.
  11. If sexually active, willing to use barrier contraception during the treatment phase of the protocol.
  12. Written informed consent and any locally required authorization (e.g., Social security for France (Health Insurance)) obtained from the patient prior to performing any protocol-related procedures, including screening evaluations.
  13. Patient willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.

Exclusion Criteria:

  1. Body Mass Index (BMI) ≥ 30.
  2. Evidence of brain metastasis.
  3. Patient seropositive for HIV and/or hepatitis B antigen positive and/or Hepatitis C antibody.
  4. Patient with history of autoimmune disease with the exception of vitiligo, psoriasis and controlled diabetes.
  5. Active suspected or prior documented autoimmune disease (including inflammatory bowel disease, celiac disease, irritable bowel syndrome, Wegener's granulomatosis and Hashimoto's thyroiditis).
  6. Patient with history of another malignancy, except for the following: skin cancers (melanoma excluded), previously treated cancer with no sign of disease for at least 3 years.
  7. Patient with concurrent infection or concurrent chronic or acute illness such as pulmonary (asthma or Chronic obstructive pulmonary disease (COPD)), cardiac (NYHA class III or IV) or hepatic disease, or other illness considered by the principal investigator to constitute an unwarranted high risk for investigational drug administration will be excluded.
  8. Chronic systemic corticosteroid use within 4 weeks of the first administration of SXL01 (more than 2 weeks for a dose > 0.5 mg/kg of prednisolone).
  9. Treatment with any hormonal therapy or androgen antagonist, including flutamide, bicalutamide, nilutamide, ketoconazole, diethylstilbestrol, Abiraterone, or enzalutamide, within 4 weeks of the first administration with the exception of gonadotropin-releasing hormone (GnRH) agonists.
  10. Patients requiring a continuous curative anti-coagulant treatment.
  11. Patients requiring a continuous bisphosphonate or denosumab treatment at inclusion. Note: the use of bisphosphonate and denosumab during the course of the study will be allowed.
  12. Planned to initiate any other anti-tumor therapies during the study.
  13. Radiation therapy or surgery within 4 weeks of the first administration of SXL01.
  14. Mental impairment (psychiatric illness/social situations) that may compromise the ability of the patient to give informed consent and comply with the requirements of the study.
  15. Patient who has forfeited his/her freedom by administrative or legal award or who is under guardianship.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02866916


Contacts
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Contact: Jean-Pierre DELORD, MD, PhD +33 5 31 15 51 00 delord.jean-pierre@iuct-oncopole.fr

Locations
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France
Institut Claudius Regaud Not yet recruiting
Toulouse, France, 31059
Contact: Jean-Pierre DELORD, MD, PhD    +33 53 15 51 00    delord.jean-pierre@iuct-oncopole.fr   
Principal Investigator: Jean-Pierre DELORD, MD, PhD         
Sponsors and Collaborators
Institut Claudius Regaud

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Responsible Party: Institut Claudius Regaud
ClinicalTrials.gov Identifier: NCT02866916     History of Changes
Other Study ID Numbers: 16GENH01
First Posted: August 15, 2016    Key Record Dates
Last Update Posted: November 25, 2016
Last Verified: November 2016

Additional relevant MeSH terms:
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Prostatic Neoplasms
Prostatic Neoplasms, Castration-Resistant
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases